Genes governing the expression of xenotropic murine leukemia viruses (X-MuLV) differ strikingly among inbred strains of mice. Two distinct loci affect the dominant expression of infectious viruses of NZB mice in crosses with other strains whereas expression of F/St infectious virus is markedly suppressed by a single locus in similar crosses. In addition, the tissue distribution of NZB infectious virus was shown to be bone marrow-spleen-thymus whereas in F/St mice infectious virus was found in thymus-marrow-spleen. Expression of two cell surface antigens, XenCSA and GIX, coded for by endogeneous X-MuLV, was shown to be influenced by different genes in crosses between C57BL/6 and DBA/2 or C3H mice: identical loci affect XenCSA levels in both crosses but different genes affect GIX expression in the DBA/2 and C3H crosses. XenCSA expression on T cells is enhanced by treatment with PHA or Con A. Finally, development of lymphoma and paralyses in NFS mice infected with wild mouse ecotropic MuLV was shown to be preceeded by the appearance of recombinant MuLV in splenic but not thymic tissues.